灰色数列预测模型在成骨细胞体外培养中的应用

目的：灰色模型是运用一定的数学方法使信息不完全明确的系统经数据处理后能得到较明确结果的一种数学预测模型，体外细胞培养的影响因素较多，属于信息不完全明确的灰色系统，故运用灰色GM（1，1）模型对成骨细胞增殖、分化的变化规律进行预测，验证模型在体外细胞培养中的可应用性。方法：实验于2005—11／2006—03在广东医学院药理教研室完成。①实验过程：应用酶序列消化分离培养法培养新生大鼠颅骨成骨细胞；用MTT法测定体外培养成骨细胞在不含血清培养液A值，以了解成骨细胞的增殖情况；对硝基苯磷酸盐法观察体积分数为0．01的胎牛血清培养液对体外培养成骨细胞分泌碱性磷酸酶活性的影响，代表成骨细胞的分化情况。②灰色GM（1，1）模型建立：运用灰色系统理论，通过SAS8．1软件对体外培养成骨细胞MTT值和碱性磷酸酶OT值进行分析和预测。结果：运用灰色系统理论的后验差检验方法对模型进行检验，MTT这一指标的平均相对误差为4．4％，碱性磷酸酶这一指标的平均相对误差为7．04％，后验差比值为0．048和0．315，综合评定该模型为“好”。结论：灰色GM（1，1）模型对体外培养成骨细胞MTT值和碱性磷酸酶的OT值变化的预测精度高，结果可靠。体外培养成骨细胞MTT值和碱性磷酸酶的OT值的变化可用灰色GM（1，1）模型进行预测。     

Comparison of enoxaparin and unfractionated heparin in endovascular interventions for the treatment of peripheral arterial occlusive disease: a randomized controlled trial

Summary. Background: Although unfractionated heparin (UFH) is an effective antithrombotic agent in endovascular interventions for the treatment of peripheral occlusive arterial disease (PAOD), it produces a highly variable anticoagulant response. Intravenous (i.v.) enoxaparin might be an effective and safe alternative. Patients and methods: In a prospective, open‐label, randomized, single‐center trial, 210 patients with PAOD (Fontaine stage IIb to IV) were randomly assigned in a 1 (UFH): 2 (enoxaparin) fashion to receive an i.v. bolus of 60 units UFH per kg body weight or 0.5 mg enoxaparin per kg body weight, respectively, before endovascular intervention. The primary composite endpoint assessed the clinical performance of enoxaparin by comparing the peri‐interventional rate of thromboembolia/occlusion (efficacy) of endovascularly reconstructed areas, of bleeding according to the Global Utilization of Streptokinase and t‐PA for Occluded Coronary Arteries (GUSTO) criteria (safety) and of any necessary re‐intervention for any percutaneous transluminal angioplasty (PTA)‐related bleeding. The secondary endpoint evaluated anti‐factor (F)Xa levels during intervention. Results: The primary composite endpoint showed a better performance of enoxaparin (10.5% vs. 2.5% absolute difference – 8.0%; P < 0.05). The concomitant use of acetylsalicylic acid (ASA) significantly (P < 0.05) increased the risk of a complication in the UFH group, but not in the enoxaparin group. Within 15 min, anti‐Xa levels were reached by 63.7% of patients treated with enoxaparin and only by 39.1% with UFH. Conclusion: Enoxaparin has a better performance than UFH in endovascular interventions for the treatment of PAOD. In patients with concomitant use of ASA, the risk of complications with UFH increases significantly compared with enoxaparin.     

Angiogenic factors stimulate mast-cell migration

Mast cells accumulate at sites of angiogenesis. The factor(s) that control mast-cell recruitment at these sites have yet to be defined. We sought to determine if angiogenic factors result in mast-cell chemotaxis. In this study, we observed that platelet-derived growth factor-AB (PDGF-AB), vascular endothelial cell growth factor (VEGF), and basic fibroblast growth factor (bFGF) each cause directed migration of murine mast cells at picomolar concentrations, with a typical bell- shaped dose-response curve. Another potent angiogenic factor, platelet- derived endothelial cell growth factor (PD-ECGF), appears to promote chemokinesis of mast cells, whereas tumor necrosis factor-alpha, a weak angiogenic factor, is less robust but still functions as a mast cell chemotactic factor. Epidermal growth factor (EGF), a growth factor with minimal angiogenic properties, was ineffective as a mast cell chemotactic factor. A checkerboard analysis confirmed the directional chemotactic response of PDGF-AB, VEGF, and bFGF, while indicating the chemokinetic response induced by PD-ECGF. Cross-desensitization of growth-factor-induced directed migration was observed between PDGF-AB and bFGF, and also between PDGF-AB and PD-ECGF. Tyrosine kinase- inhibitor genistein effectively dampened the chemotactic responses, whereas pertussis toxin had no effect. In summary, our findings suggest that factors known to act on endothelial cells and stimulate neovascularization may simultaneously serve to recruit mast cells to these sites. The local accumulation of mast cells is believed to facilitate new vessel formation through complex cell:cell interactions.     

Reduced-intensity hematopoietic cell transplantation in older patients with AML/MDS: umbilical cord blood is a feasible option for patients without HLA-matched sibling donors

Umbilical cord blood (UCB) has increased access to hematopoietic cell transplantation (HCT) for patients without HLA-matched sibling donors (MSD). We compared outcomes of HCT using MSD (N=38) or UCB (N=60) among older patients (age ≥ 55 years) with AML or myelodysplastic syndromes (MDS). All patients received a reduced intensity regimen consisting of CY, fludarabine and 200 cGy TBI. Median age at HCT was 63 years for MSD and 61 years for UCB recipients. Among UCB recipients, 95% received two UCB units and 88% received 1-2 locus HLA-mismatched units to optimize cell dose. OS at 3-years was 37% for MSD and 31% for UCB recipients (P=0.21). On multivariate analysis, donor source (MSD vs UCB) did not impact risks of OS, leukemia-free survival and relapse or treatment-related mortality. UCB is feasible as an alternative donor source for reduced-intensity conditioning HCT among older patients with AML and MDS who do not have a suitable MSD.     

Erythroid failure in Diamond-Blackfan anemia is characterized by apoptosis

Programmed cell death, also known as apoptosis, is frequently initiated when cells are deprived of specific trophic factors. To investigate if accelerated apoptosis contributes to the pathogenesis of Diamond- Blackfan anemia (DBA), a rare pure red blood cell aplasia of childhood, we studied the effect of erythropoietin (epo) deprivation on erythroid progenitors and precursors from the bone marrow of DBA patients as compared with hematologically normal controls. Apoptosis in response to epo deprivation was evaluated by enumeration of colony-forming unit- erythroid (CFU-E)- and burst-forming unit-erythroid (BFU-E)-derived colonies in plasma clot semisolid culture and by the identification of typical DNA oligosomes by gel electrophoresis from marrow mononuclear cells in liquid culture. In all DBA patients there was a marked decrease in CFU-E- and BFU-E-derived colony formation compared with normal controls at comparable time points of epo deprivation, with a complete loss of CFU-E-derived colonies in semisolid culture by 9 hours of epo deprivation versus 48 hours in controls. The BFU-E-derived colony response to epo deprivation displayed a similar pattern of decrement. Apoptotic changes assessed by the presence of characteristic DNA fragmentation began in the absence of epo deprivation and were readily detected within 3 hours of epo deprivation in DBA cultures versus 9 hours in controls. We conclude that DBA is characterized by accelerated apoptosis as measured by the loss of erythroid progenitor clonogenicity and increased progenitor and precursor DNA fragmentation leading to the formation of characteristic oligosomes, consistent with an intrinsic erythroid-progenitor defect in which increased sensitivity to epo deprivation results in erythroid failure.